Table 3.
Ingenuity Pathway Analysis of differentially expressed genes from the fetal sheep astrocytes whole transcriptome analysis: naïve and second hit astrocytes after modulation of α7nAChR signaling.
| comparison | # genes | Top 10 signaling pathways | -log(p-value) |
|---|---|---|---|
| Single hit: LPS100 vs. Control | 1835 | NF-κB Signaling | 15.8 |
| Role of Pattern Recognition Receptors in Recognition of Bacteria & Viruses | 14 | ||
| Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis | 13.7 | ||
| Dendritic Cell Maturation | 13 | ||
| Neuroinflammation Signaling Pathway | 12.8 | ||
| Role of IL-17A in Arthritis | 12.2 | ||
| Activation of IRF by Cytosolic Pattern Recognition Receptors | 11.6 | ||
| Death Receptor Signaling | 11.3 | ||
| Th1 and Th2 Activation Pathway | 10.7 | ||
| TREM1 Signaling | 10.5 | ||
| Single hit: LPS100+A10 vs. Control | 1725 | NF-κB Signaling | 14.7 |
| Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis | 13.7 | ||
| Role of Osteoblasts, Osteoclasts and Chondrocytes in Rheumatoid Arthritis | 13.1 | ||
| Granulocyte Adhesion and Diapedesis | 12.7 | ||
| Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses | 12.5 | ||
| Hepatic Cholestasis | 12.5 | ||
| Toll-like Receptor Signaling | 11.7 | ||
| Axonal Guidance Signaling | 11.5 | ||
| IL-10 Signaling | 11.1 | ||
| Neuroinflammation Signaling Pathway | 10.7 | ||
| Single hit: LPS100+B100 vs. Control | 1744 | NF-κB Signaling | 16.8 |
| Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis | 16 | ||
| Dendritic Cell Maturation | 15.9 | ||
| Neuroinflammation Signaling Pathway | 15 | ||
| Role of Pattern Recognition Receptors in Recognition of Bacteria & Viruses | 14.8 | ||
| TREM1 Signaling | 12.8 | ||
| Role of IL-17A in Arthritis | 12.7 | ||
| T Cell Exhaustion Signaling Pathway | 11.9 | ||
| Toll-like Receptor Signaling | 11.8 | ||
| PI3K Signaling in B Lymphocytes | 11.6 | ||
| Single hit: LPS100+A10 vs. LPS100 | 273 | Granulocyte Adhesion and Diapedesis | 6.23 |
| Pathogenesis of Multiple Sclerosis | 5.81 | ||
| Agranulocyte Adhesion and Diapedesis | 5.12 | ||
| Th1 and Th2 Activation Pathway | 4.45 | ||
| Th2 Pathway | 4.4 | ||
| LPS/IL-1 Mediated Inhibition of RXR Function | 3.81 | ||
| NF-κB Signaling | 3.71 | ||
| Role of Osteoblasts, Osteoclasts and Chondrocytes in Rheumatoid Arthritis | 3.63 | ||
| Inhibition of Angiogenesis by TSP1 | 3.33 | ||
| STAT3 Pathway | 3.25 | ||
| Single hit: LPS100+B100 vs. LPS100 | 0 | ||
| Single hit: | 292 | Granulocyte Adhesion and Diapedesis | 5.25 |
| LPS100+A10 vs. LPS100+B100 | Agranulocyte Adhesion and Diapedesis | 4.99 | |
| LPS/IL-1 Mediated Inhibition of RXR Function | 4.38 | ||
| Hepatic Fibrosis / Hepatic Stellate Cell Activation | 4.35 | ||
| NF-κB Signaling | 4.33 | ||
| Role of Osteoblasts, Osteoclasts and Chondrocytes in Rheumatoid Arthritis | 4.18 | ||
| Pathogenesis of Multiple Sclerosis | 3.97 | ||
| STAT3 Pathway | 3.94 | ||
| p53 Signaling | 3.57 | ||
| Sirtuin Signaling Pathway | 3.36 | ||
| LPS100: single hit vs. second hit | 3761 | Hepatic Fibrosis / Hepatic Stellate Cell Activation | 10.7 |
| Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes | 7.69 | ||
| Leukocyte Extravasation Signaling | 6.82 | ||
| Signaling by Rho Family GTPases | 6.16 | ||
| Iron homeostasis signaling pathway | 6.02 | ||
| LXR/RXR Activation | 5.36 | ||
| Epithelial Adherens Junction Signaling | 4.99 | ||
| Role of Osteoblasts, Osteoclasts and Chondrocytes in Rheumatoid Arthritis | 4.96 | ||
| Axonal Guidance Signaling | 4.91 | ||
| Tec Kinase Signaling | 4.82 | ||
| LPS100+A10: single hit vs. second hit | 3307 | Hepatic Fibrosis / Hepatic Stellate Cell Activation | 13 |
| Leukocyte Extravasation Signaling | 8.79 | ||
| Neuroinflammation Signaling Pathway | 7.18 | ||
| Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes | 6.99 | ||
| Axonal Guidance Signaling | 6.93 | ||
| Phagosome Formation | 6.85 | ||
| Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses | 6.67 | ||
| Agranulocyte Adhesion and Diapedesis | 6.24 | ||
| GP6 Signaling Pathway | 6.1 | ||
| Granulocyte Adhesion and Diapedesis | 5.92 | ||
| LPS100+B100: single hit vs. second hit | 3860 | Hepatic Fibrosis / Hepatic Stellate Cell Activation | 8.89 |
| Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes | 8.03 | ||
| Leukocyte Extravasation Signaling | 7.26 | ||
| Epithelial Adherens Junction Signaling | 5.94 | ||
| Iron homeostasis signaling pathway | 5.78 | ||
| Signaling by Rho Family GTPases | 5.51 | ||
| Axonal Guidance Signaling | 5.18 | ||
| Endothelin-1 Signaling | 5.04 | ||
| Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis | 5.01 | ||
| Phagosome Formation | 4.99 |
Differential analysis of count data was done with the Bioconductor limma package. Differentially expressed genes were selected, based on a 1.5-fold change and an FDR < 0.05. Up regulation and down regulation represent positive and negative log2 fold changes, respectively. For details on “raw gene” level, see our GitHub repository or directly here. Bold font highlights pathways common with microglia.
Orange: positive z-score; blue: negative z-score. For further details as raw data and visualized activity patterns see GitHub.
Significant genes in astrocytes cultures at an FDR < 0.05 and a 1.5-fold change sorted on log(p-value).